Objective: The aim of this study was to explore the interactions of occupational stress and glucocorticoid receptor gene ( GR ) polymorphisms on essential hypertension (EH) among Chinese railway workers. Methods: A case-control study was conducted with 196 EH cases and matched controls from male railway employees. Occupational stress was scaled by a validated Chinese version of the Occupational Stress Inventory. Information on risk factors for hypertension, including smoking, alcohol consumption, family hypertension history and body mass index, was collected by face to face interviews. Genotypes of GR BCL1 and G678S genes were determined with PCR-RFLP. Conditional logistic regression was applied to examine the interactions of occupational stress and GR gene polymorphisms with adjustment for potential confounders. Results: A positive relationship was observed in the CG/GG genotype compared with the CC genotype in the GRBCL1 gene. The interaction between the GRBCL1 gene and occupational stress was statistically significant on EH. The odds ratio (OR) was 1.56 (95% CI: 0.93, 2.63) when comparing the CG/GG genotype of the GRBCL1 gene with low/medium personal strain with the CC genotype with low/medium strain, whereas the OR was 3.43 (95% CI: 1.45, 8.12) when comparing the same genotype with high strain with the same reference. A similar pattern of association was observed for the CG/GG genotype of the GRBCL1 gene with low/medium occupational stress (OR=1.32, 95% CI: 0.76, 2.30) and with high occupational stress (OR=3.58, 95% CI: 1.60, 8.02). Conclusions: This study suggests that the CG/GG genotype in GRBCL1 possibly interacts with occupational stress in increasing the risk for essential hypertension in the railway workers, but more studies with larger samples are needed to confirm the finding.(J Occup Health 2013; 55: 349-358)